title: Human cardiac stem cells with reduced notch signaling show enhanced therapeutic potential in a rat acute infarction model.
abstract: BACKGROUND
  Because human cardiac stem cells (CSC) have regeneration potential in damaged cardiac tissue, there is increasing interest in using them in cell-based therapies for cardiac failure. However, culture conditions, by which CSCs are expanded while maintaining their therapeutic potential, have not been optimized. We hypothesized that the plating cell-density would affect proliferation activity, differentiation and therapeutic potential of CSCs through the Notch signaling pathway.
  
  
  RESULTS
  Human CSCs were plated at 4 different densities. The population doubling time, C-KIT positivity, and dexamethasone-induced multidifferentiation potential were examined in vitro. The therapeutic potential of CSCs was assessed by transplanting them into a rat acute myocardial infarction (AMI) model. The low plating density (340cells/cm(2)) maintained the multidifferentiation potential with greater proliferation activity and C-KIT positivity in vitro. On the other hand, the high plating density (5,500cells/cm(2)) induced autonomous differentiation into endothelial cells by activating Notch signaling in vitro. CSCs cultured at low or high density with Notch signal inhibitor showed significantly greater therapeutic potential in vivo compared with those cultured at high density.
  
  
  CONCLUSIONS
  CSCs cultured with reduced Notch signaling showed better cardiomyogenic differentiation and therapeutic potentials in a rat AMI model. Thus, reducing Notch signaling is important when culturing CSCs for clinical applications.
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine.
authors.forename: Takenori
authors.initials: T
authors.lastname: Matsuda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Satsuki
authors.initials: S
authors.lastname: Fukushima
authors.forename: Satoru
authors.initials: S
authors.lastname: Kitagawa-Sakakida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akimaru
authors.forename: Miki
authors.initials: M
authors.lastname: Horii-Komatsu
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kawamoto
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Saito
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asahara
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D002648:Child; D005260:Female; D064593:Heterografts; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011923:Rats, Nude; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D051880:Receptors, Notch